Passive transfer of high titered anti-viral neutralizing IgG, known to confer sterilizing immunity in pig-tailed monkeys, has been used to determine how soon following virus exposure, neutralizing antibodies (NAbs) must be present to block an SIV/HIV chimeric virus (SHIV) infection. Sterilizing protection was achieved in three of four macaques receiving neutralizing IgG 6 hours following intravenous SHIV inoculation as monitored by PCR analyses of and attempted virus isolations from plasma, PBMC and lymph node specimens. In the fourth animal, the production of progeny virus was suppressed for more than 4 weeks. A delay in transferring NAbs until 24 hours post virus challenge resulted in infection in two of two monkeys. These results suggest that even if a vaccine, capable of eliciting broadly reactive NAbs against primary HIV-1 were at hand, the antibodies generated must remain at, or rapidly achieve, high levels within a relatively short period following exposure to virus to prevent the establishment of a primate lentivirus infection. MHC loci encode highly polymorphic molecules involved in the presentation of self and non-self peptides to cells of the adaptative and innate immune systems. Although variable, MHC-E genes are well conserved among primates and provide signals to natural killer cells. In this study, we sequenced and analyzed MHC-E alleles of pig-tailed macaques (Macaca nemestrina), a non-human primate used for HIV pathogenesis and vaccine studies. Among a group of seven macaques, the characterization of 8 Mane-E alleles revealed an increased number of polymorphic sites compared to human HLA-E alleles. Phylogenetic analyses of MHC-E alleles from pig-tailed macaque, rhesus monkey (Macaca mulatta) and cynomolgus macaque (Macaca fascicularis) demonstrated that the three macaque species shared 6 families of macaque MHC-E alleles and indicated that these families existed in the common ancestor 5.5 million years ago. Polymorphic Mane-E sites were not concentrated within the peptide binding pockets but were distributed throughout the entire ORF. The peptide-binding domain of Mane-E is similar to its human analogue, and peptide substrates theoretically capable of binding to Mane-E molecules were found in the leader sequence of classical Mane-A and -B molecules. Additionally, the polymorphic amino-acids located in the alpha 1 and alpha 2 domains of Mane-E molecules have side chains expected to be oriented toward solvent, away from the peptide binding groove, suggesting that some of them (positions 19, 73, 79 and 145) might be available for interaction with polymorphic receptors of NK cells.